Zinc is an important
trace element shown to play an important structural and functional role in
pancreas, being required by endocrine islet cells for insulin secretion and by
exocrine acinar cells as pancreatic juice component1,2 . ZnT8 is a member of the
SLC30A family of zinc transporters involved packaging and secretion insulin in
response to glucose, suggesting a possible role in regulating glycemia. ZnT8 in
studies identified polymorphisms in the ZnT8 gene conferring increased type 2
diabetes risk1,2 . Our study aims to investigate
the zinc and zinc transporter regulation in a type 2 diabetic db/db mice model
compared to the age matched control (C57BL6J) mice. Methods. Zinc was measured
using flame atomic absorption spectrometry and Zinpyr-1 staining (labile pool)
and Immunofluorescence was done using frozen sections of pancreas of control
and diabetic mice and were stained using zinc transporter antibodies. Results.
Db/db mice livers at 14 weeks showed significant reduction of zinc
concentration compared to its age matched controls livers (49%, p<0.05,
n=5). Db/db mice pancreas also showed significant reduction in zinc in the
early diabetic mice (55%, p<0.05 n=6), diabetic (40%, p=0.0013, n=6) and
chronic diabetic (26%, p=0.002,n=5) respectively compared to its aged matched
controls. Zinc concentration in the plasma of the db/db mice were elevated
compared to the controls. Pancreatic islets of 4, 10 and 18 weeks mice showed
down regulation of efflux transporter ZnT8 and upregulation of influx
transporter ZIP14 when counterstained with glucagon. Conclusion. The
subcellular distribution of the zinc transporters ZnT8 and ZIP14 in 4, 10 and
18 week old mice db/db mice pancreas is altered during the progression of
diabetes thereby affecting the zinc availability and regulation. Further
experiments will be carried to investigate the regulation of these transporters
using quantitative real time PCR.